Female reproductive traits and late-life hormone-sensitive cancer risk: a Mendelian randomization study
Menée à l'aide d'une méthode de randomisation mendélienne et de plusieurs séries de données, cette étude analyse l'association entre des caractéristiques du système reproducteur féminin (vieillissement ovarien, réserve ovarienne et antécédents obstétriques) et le risque de cancer hormono-dépendant
Ovarian reserve is a crucial component of female reproductive traits. However, the possible causal effects between ovarian reserve and hormone-sensitive cancers remain incompletely understood. Two-sample Mendelian randomization analyses (MR) were performed to assess potential causal effects of reproductive traits on hormone-sensitive cancers. In addition, multivariable MR was applied to determine the potential mediation effects of reproductive traits on hormone-sensitive cancers. A one SD incremental increase in the anti-Müllerian hormone (AMH) level was associated with a higher risk of endometrial cancer (OR = 1.27, 95% CI = 1.05–1.54) but a lower risk of breast cancer (OR = 0.80, 95% CI = 0.69–0.94). Each 1-year incremental increase in age at natural menopause was associated with higher risks of breast (OR = 1.04, 95% CI, 1.02–1.05), ovarian (OR = 1.03, 95% CI, 1.01–1.05), and endometrial cancers (OR = 1.07, 95% CI, 1.04–1.09). Nulliparity increased the risk of breast cancer (OR = 1.07, 95% CI, 1.05–1.09). An elevated AMH level was indirectly associated with endometrial cancer risk with 2.67% of the effect attributed to later age at natural menopause (per 1-year increase). Each 1-year incremental increase in age at menarche was indirectly associated with endometrial cancer risk with 4.71% of the effect attributed to later age at natural menopause. The findings herein highlight AMH as a potential key biological marker for endometrial and breast cancer risk. Identifying natural menopause as a key modulator may enhance our understanding of the mechanisms underlying hormone-sensitive cancers.
Cancer Prevention Research , résumé, 2026